本文選題：BCL11A + 淋巴結(jié)受累　； 參考：《重慶醫(yī)科大學(xué)》2017年碩士論文

【摘要】：宮頸癌是一種女性常見(jiàn)腫瘤,對(duì)女性身心健康造成了極大危害,近年來(lái)其發(fā)病率及死亡率在全球范圍內(nèi)呈上升趨勢(shì)。雖然人類在宮頸癌HPV疫苗的研發(fā)中已有重大突破,但是全球范圍內(nèi),宮頸癌依然是第四大癌癥,其死亡率僅次于乳腺癌。B細(xì)胞淋巴瘤11A(B-cell CLL/lymphoma 11A,BCL11A),其同源基因Evi9(ecotropic viral integration site 9)最初發(fā)現(xiàn)于骨髓性白血病BXH2小鼠中,作為逆轉(zhuǎn)錄病毒的插入位點(diǎn),并與BCL6蛋白相互作用[1]。BCL11A在非實(shí)體瘤如白血病、淋巴瘤等造血與淋巴組織腫瘤中發(fā)揮重要作用[2,6]。最近有研究發(fā)現(xiàn),BCL11A在實(shí)體瘤如三陰性乳腺癌及非小細(xì)胞肺癌中也發(fā)揮著重要作用[3,4],但是BCL11A在宮頸癌中的作用尚未有報(bào)道,本研究將主要通過(guò)組織及細(xì)胞水平研究BCL11A在宮頸癌中的作用及對(duì)其機(jī)制進(jìn)行初步探索。第一部分bcl11a在宮頸癌組織中的表達(dá)及其臨床意義目的:研究bcl11a在宮頸癌組織及癌旁正常組織中的表達(dá)情況,并分析其差異表達(dá)與臨床病理因素之間的關(guān)系及臨床意義。方法:結(jié)合tcga數(shù)據(jù)庫(kù),利用生物信息學(xué)分析bcl11a在不同癌癥組織及相應(yīng)正常組織中的表達(dá),并分析bcl11a的表達(dá)與宮頸癌患者預(yù)后的關(guān)系。收集62例宮頸癌組織及相對(duì)應(yīng)的癌旁正常組織,制作成石蠟切片,并通過(guò)免疫組織化學(xué)法檢測(cè)bcl11a蛋白在宮頸癌組織和癌旁正常組織中的表達(dá),并結(jié)合患者資料,分析bcl11a的表達(dá)與臨床病理因素之間的關(guān)系。結(jié)果:生物信息學(xué)分析得知bcl11a在宮頸癌及癌旁正常組織中存在差異;在收集的62例宮頸癌組織及癌旁正常組織中均檢測(cè)到了bcl11a的表達(dá),其中有50例宮頸癌組織檢測(cè)到bcl11a的高表達(dá)(80.6%);有13例癌旁正常組織中檢測(cè)到bcl11a的高表達(dá)(21%)。bcl11a蛋白在宮頸癌組織及癌旁正常組織中的表達(dá)存在差異(p0.01);bcl11a蛋白的表達(dá)與宮頸癌患者的年齡(p=0.436),腫瘤大小(p=0.734)以及淋巴結(jié)轉(zhuǎn)移數(shù)目(p=0.439)等無(wú)關(guān);與未出現(xiàn)淋巴結(jié)轉(zhuǎn)移(n0)的宮頸癌患者相比,在出現(xiàn)淋巴結(jié)轉(zhuǎn)移(n1-3)的宮頸癌患者中bcl11a蛋白的表達(dá)較高(p0.05);bcl11a表達(dá)較高的宮頸癌患者的總生存期要優(yōu)于bcl11a表達(dá)較低的宮頸癌患者。在宮頸癌組織中,bcl11a的表達(dá)主要定位于細(xì)胞核,在宮頸癌正常組織中,bcl11a的表達(dá)主要定位于細(xì)胞質(zhì)中。結(jié)論:bcl11a在宮頸癌組織中高表達(dá),在癌旁正常組織中表達(dá)較低;bcl11a的表達(dá)與宮頸癌患者的淋巴結(jié)受累情況相關(guān),即出現(xiàn)淋巴結(jié)轉(zhuǎn)移的患者bcl11a的表達(dá)較高;在疾病發(fā)展的早期,bcl11a表達(dá)高的宮頸癌患者的總生存期要優(yōu)于bcl11a表達(dá)低的宮頸癌患者,但并不能作為獨(dú)立的宮頸癌患者總生存期的判定指標(biāo);在宮頸癌組織中bcl11a的表達(dá)主要定位于在細(xì)胞核中,而在癌旁正常組織中,bcl11a的表達(dá)主要定位于細(xì)胞質(zhì)中。第二部分干擾BCL11A基因的表達(dá)對(duì)宮頸癌細(xì)胞相關(guān)生物學(xué)特性的影響目的:研究BCL11A基因?qū)m頸癌細(xì)胞周期、凋亡以及增殖能力的影響方法:設(shè)計(jì)并合成干擾BCL11A基因的si-RNA序列,篩選出干擾效果最佳序列;通過(guò)細(xì)胞轉(zhuǎn)染靶向沉默BCL11A基因在宮頸癌C33A細(xì)胞中的表達(dá),通過(guò)流式細(xì)胞技術(shù)檢測(cè)沉默BCL11A后,C33A細(xì)胞周期及凋亡的變化情況;使用CCK-8試劑盒檢測(cè)C33A細(xì)胞增殖能力的變化。結(jié)果:BCL11A在宮頸癌C33A細(xì)胞中表達(dá)較高,在Hela,Siha和Ca Ski細(xì)胞中表達(dá)較低;與siRNA2和siRNA3相比,siRNA1的干擾效率最好;與blank control組(6.56±0.59%)和NC組(7.85±0.47%)相比,siRNA-BCL11A組(28.45±4.07%)的細(xì)胞凋亡比率明顯升高,且具有統(tǒng)計(jì)學(xué)意義(P0.05),但是三組的細(xì)胞周期變化及增殖能力無(wú)明顯差異。結(jié)論:BCL11A在宮頸癌細(xì)胞中的表達(dá)水平可能與宮頸癌細(xì)胞的類型有關(guān),在C33A細(xì)胞中沉默BCL11A基因的表達(dá)對(duì)C33A細(xì)胞的細(xì)胞周期及增殖能力沒(méi)有影響,但是能夠促進(jìn)C33A細(xì)胞的凋亡。
[Abstract]:Cervical cancer is a common female tumor, which has caused great harm to the physical and mental health of women. In recent years, the incidence and mortality of the cervical cancer are rising worldwide. Although human beings have made great breakthroughs in the research and development of HPV vaccine for cervical cancer, cervical cancer is the fourth major cancer in the world, and the death rate is second to.B of breast cancer. Cell lymphoma 11A (B-cell CLL/lymphoma 11A, BCL11A), and its homologous gene Evi9 (ecotropic viral integration site 9) originally found in BXH2 mice with myeloid leukemia, as a retrovirus insertion site, and interacting with the BCL6 protein in non solid tumors such as leukemia, lymphoma and other hematopoietic and lymphoid tissue tumors. [2,6]. has recently shown that BCL11A also plays an important role in solid tumor such as three negative breast cancer and non-small cell lung cancer, [3,4], but the role of BCL11A in cervical cancer has not been reported. This study will mainly study the role and mechanism of BCL11A in cervical cancer by tissue and cell level. To explore the expression of Bcl11A in cervical cancer tissue and its clinical significance: To study the expression of Bcl11A in cervical cancer tissues and normal tissues adjacent to cancer, and to analyze the relationship and clinical significance between the differential expression and the clinicopathological factors. Methods: combining the TCGA data base and using bioinformatics to analyze Bcl11A in different carcinomas. The expression of Bcl11A and the prognosis of cervical cancer patients were analyzed. 62 cases of cervical cancer tissues and corresponding normal paracancerous tissues were collected, and paraffin sections were made, and the expression of Bcl11A protein in cervical cancer tissues and normal tissues was detected by immunohistochemistry and combined with the patients. Data, analysis of the relationship between the expression of Bcl11A and the clinicopathological factors. Results: bioinformatics analysis showed that Bcl11A was different in the normal tissues of cervical cancer and adjacent to cancer, and the expression of Bcl11A was detected in 62 cases of cervical cancer tissues and normal tissues adjacent to cancer, of which 50 cases of cervical cancer detected the high expression of Bcl11A (8 0.6%): the expression of high expression of Bcl11A (21%).Bcl11a protein in cervical cancer tissues and adjacent normal tissues was found in 13 normal para cancerous tissues (P0.01), and the expression of Bcl11A protein was not related to the age of cervical cancer (p=0.436), the size of the tumor (p=0.734) and the number of lymph node metastases (p=0.439), and no lymph nodes were found. The expression of Bcl11A protein in cervical cancer patients with metastatic (n1-3) metastasis (N0) was higher (P0.05) than that of cervical cancer patients with lymph node metastasis (P0.05); the total survival time of the patients with higher Bcl11A expression was better than that of the lower Bcl11A. In cervical cancer, the expression of Bcl11A was mainly located in the nucleus and in the normal cervical cancer. In the tissue, the expression of Bcl11A is mainly located in the cytoplasm. Conclusion: Bcl11A is highly expressed in cervical cancer tissues and low in normal tissues adjacent to cancer; the expression of Bcl11A is associated with lymph node involvement in patients with cervical cancer, that is, the expression of Bcl11A is higher in patients with lymph node metastasis, and in the early stage of the development of the disease, the high expression of the uterus in Bcl11A is expressed. The total survival time of cervical cancer patients is better than that of Bcl11A with low expression of cervical cancer, but it can not be used as a criterion for the determination of the total survival time of the patients with cervical cancer; the expression of Bcl11A in the cervical cancer tissues is mainly located in the nucleus, while in the normal tissues adjacent to the cancer, the expression of Bcl11A is mainly located in the cytoplasm. The second part interferes with BCL. The effect of the expression of 11A gene on the biological characteristics of cervical cancer cells: To study the effect of BCL11A gene on the cell cycle, apoptosis and proliferation of cervical cancer cells: to design and synthesize si-RNA sequences that interfere with BCL11A gene, to screen out the best sequence of interference effect, and to transfect target silent BCL11A gene to C33A in cervical cancer through cell transfection. The expression in the cell was detected by flow cytometry. The changes in the cycle and apoptosis of C33A cells after BCL11A were detected. The proliferation ability of C33A cells was detected by CCK-8 kit. Results: BCL11A was highly expressed in the C33A cells of cervical cancer and low in Hela, Siha and Ca Ski cells; the interference compared with siRNA2 and siRNA3. The efficiency was the best. Compared with group blank control (6.56 + 0.59%) and group NC (7.85 + 0.47%), the percentage of apoptosis in group siRNA-BCL11A (28.45 + 4.07%) was significantly higher and had statistical significance (P0.05), but there was no significant difference in the cell cycle and proliferation ability of the three groups. Conclusion: the expression level of BCL11A in cervical cancer cells may be associated with cervical cancer. The type of cell is related to the silence of the expression of BCL11A gene in C33A cells. It has no effect on the cell cycle and proliferation of C33A cells, but can promote the apoptosis of C33A cells.

【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R737.33

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